Probiotics Helpful Against Late-Onset Sepsis in Preemies: Meta-analysis

By Megan Brooks

February 16, 2016

NEW YORK (Reuters Health) - Giving preterm babies probiotics reduces the risk of late-onset sepsis (LOS), according to a new meta-analysis of 37 studies.

LOS is a major cause of illness and death in preterm infants and new strategies to reduce LOS are "urgently needed," the authors note in their paper, online February 12 in Pediatrics. One possible strategy is probiotic supplementation.

"Animal research and in vitro studies have shown that probiotics improve gut barrier function, inhibit gut colonization with pathogenic bacteria, improve colonization with healthy commensals, protect from enteropathogenic infection through production of acetate, enhance innate immunity, and increase maturation of the enteric nervous system, all of which have the potential to decrease the risk of LOS in preterm infants," Dr. Shripada Rao, from Prince Margaret Hospital for Children, Perth, Western Australia and colleagues point out.

Yet, two recent meta-analyses - one a Cochrane analysis of 19 studies and the other of 17 studies - failed to show a statistically significant reduction in LOS in preterm infants given probiotics. The analysis by Dr. Rao's group included 37 studies and did show a benefit of probiotics (versus placebo or no probiotic) on LOS.

"Ours is the largest meta-analysis on this topic so far. In fact, to our knowledge, it is the largest meta-analysis of randomized trials in neonatal medicine. For the first time, probiotics have been shown to reduce the incidence of LOS in preterm neonates in a meta-analysis," Dr. Rao told Reuters Health by email.

Pooled results from all 37 studies (9,416 infants) gave a relative risk of LOS with probiotics of 0.86, with a number needed to treat of 44. There were 675 cases of LOS in 4,852 preterm infants who received probiotics (13.9%) versus 744 cases in 4,564 infants who received placebo/no probiotic (16.3%). "The results were significant even after excluding studies with high risk of bias," the authors say in their paper.

"The results were also significant in studies that included only infants with gestational age <32 weeks or birth weight <1500 g (24 studies, sample size 7175), studies where Bifidobacterium was part of the supplementation (22 studies, sample size 6069), studies where Lactobacillus was part of the supplementation (21 studies, sample size 4608), studies where single-strain probiotics were used (23 studies, sample size 5961), and studies where multiple-strain supplements were used (14 studies, sample size 3455)," they note.

The most likely reason for the difference between the current meta-analysis and the previous ones is the sample size, the researchers say.

"Our findings are not against the Cochrane 2014 analysis; they take it one step forward," Dr. Rao told Reuters Health. "The Cochrane analysis had shown a 'trend' towards benefits of probiotic supplementation in reducing LOS. Its small sample size was probably not sufficient to detect a small, but statistically and clinically significant benefit of probiotic supplementation. The sample size of our meta-analysis is 9,416, which is 4,078 more than the Cochrane analysis for this outcome."

The researchers say a limitation of their analysis is that LOS was a secondary outcome of interest in most of the studies. Also, they lacked information from 14 studies and minimal information was available on extremely preterm or extremely low birth weight babies. They also weren't able to objectively assess the effect of variables such as dosage and duration of supplementation on LOS - "highly important questions" that need to be addressed in controlled trials, they say.

Despite these limitations, they conclude, "Given the serious consequences of LOS in preterm infants, we believe that a strategy that has been shown by this largest neonatal meta-analysis to date is worth consideration by health care policymakers, clinicians, and, most importantly, the parents of preterm infants."

"Another important factor that must be considered is the fact that probiotic supplementation has been shown to reduce the risk of NEC (necrotizing enterocolitis) in preterm infants. If a simple intervention such as probiotic supplementation can reduce the risk of 2 of the most devastating conditions that affect preterm infants, it is worth paying attention," they add.

The study had no external funding and the authors have no conflicts of interest.


Pediatrics 2016.